Carnosine: Opinion from Dr. Jon Pangborn

[Guest guest]

Hello everyone,

I wrote a letter to Dr. Jon Pangborn and asked him his opinion regarding

the use of carnosine in supplements, specifically Metagenics' new Zinlori

product, which contains a low dose of carnosine (my letter is at the bottom

of this message). Following is Dr. Pangborn's reply (which he stated that

I could post to Internet Yahoo groups).

Dear :

I still have the same concerns about carnosine use as a supplement for

autistics. I have spoken to Dr. Chez directly about it. I'm aware that it

has helped many autistics, especially those with seizure conditions, and

Dr. Chez confirms that the best responses he has seen are for seizure

cases. I'm also aware of a number of disasters with its use - extreme

hyperactivity, worsening of autistic traits, and week-to month periods of

recovery after using carnosine for only one day.

Autistics are individuals who have considerable variability when it comes

to biochemistry that's on the periphery of that which pertains directly to

autism itself. Carnosine is not central to autism; it is on the periphery.

Carnosine is a peptide composed of histidine (a conditionally essential

amino acid) and beta-alanine (often a troublemaking amino acid). Some

manufacturer claims that I've seen exhibit total ignorance when they say

carnosine is histidine plus " alanine " . Alanine is fine, beta-alanine is

definitely not fine.

So, if you want to try carnosine as a nutritional option, do so with the

knowledge that adverse effects can occur. I must continue to advise against

its use by clinicians until certain analytical (lab) measurements are

negative for contraindication. Analytical contraindications for carnosine

use are: elevated carnosine and/or beta-alanine in blood/urine, and high

taurine (wasting) in urine. A further contraindication would be worsening

of the blood copper/zinc ratio with carnosine despite co-supplementation

with zinc.

You may post this on the Internet.

Jon Pangborn

________________________________________________________________________________\

_______________

________________________________________________________________________________\

_______________

Dear Dr. Pangborn,

I received your contact information from the Autism Research Institute. I

have asked this question on a few well-respected and helpful autism lists,

but no one knew the answer, so I am writing to you directly. I am a single

parent of a 6 1/2 year old son with autism, and research quite a bit (at

least a little every day). My goal is to choose the best supplements for

my son. There is a relatively new product by Metagenics called Zinlori 75

(other brands market it as PepZin), which sounds very promising for healing

the gut. Here's the link:

http://www.metagenics.com/products/catalog/detail.asp?pid=225

Back when everyone was citing a study by Dr. Chez regarding carnosine, I

found statements attributed to you (by searching on google and in a paper

by Willis Langford--see the info below), and decided NOT to try carnosine

for my son. Although I did not totally understand what was said in the

references (I do not have a medical or biochemical background), the

concerns seemed serious, so I didn't try the product.

A well-informed parent on the chelatingkids2 list posted info about

Metagenics' new Zinc/Carnosine complex. This parent has a relatively

complex understanding of biomedical and is VERY well informed. He is

really excited about this product and has posted links to a lot of studies

regarding its efficacy.

I am wondering if you still have reservations about carnosine, and

specifically what you think about the new low dose carnosine/zinc complex

(perhaps the dosage is key, and a little is Ok, as in low dose naltrexone,

or LDN). I know that some DAN! practitioners are prescribing or

recommending this product (I don't know which doctors, but listmates have

reported this). Here's a link to an article about this complex (I will

also send you the article in a separate email):

http://www.iherb.com/ulcers2.html#intro

Thank you in advance for any insight you can provide! I really appreciate

your time and expertise. Also, would it be Ok to share the information you

provide with the few lists and individuals I posted to (this included Dr.

McCandless' CSB list and chelatingkids2)?

Thanks again! :-)

From a paper entitled " Mastering Autism " by Willis S. Langford:

Dr. Pangborn, Ph. D. biochemist, has some serious reservations about Dr.

Chez's approach to carnosine supplementation (referenced below).

Dr. Pangborn has stated:

" In body tissues, carnosine is split into histidine and beta-alanine.

Beta-alanine can be a real troublemaker, and I'll get to that shortly.

Histidine is the Dr. Jekyll and Mr. Hyde part. Histidine becomes

formiminoglutamic acid (FIGlu), and FIGlu (an intermediate metabolite in

histidine catabolism in the conversion of histidine to glutamic acid, with

the formimino group being transferred to tetrahydrofolic acid) pushes the

formation of 5-formiminotetrahydrofolate. A build up of FIGlu usually

indicates a folic acid deficiency. (A test of vitamin B12 deficiency, folic

acid deficiency, liver disease, or genetic deficiency of glutamate

formiminotransferase, based on urinary excretion of FIGlu).

This is good, even though it often raises FIGlu levels in the urine and

blood of autistics. It's good because: (a) it helps remove a potential

folate trap, and ( it leads to two forms of folate that are required for

purine and purine nucleotide synthesis. One of these forms,

10-formyltetrahydrofolate, comes in just after the adenylosuccinase step

and helps " pull " the process along at a documented sticking point for some

forms of autism.

However, histidine and Carnosine are powerful carriers of copper. They

transport copper from the intestinal milieu into the portal blood, and from

there to organs and tissues in the body. And don't think you can displace

copper with zinc once the copper is on histidine--you cannot. The

equilibrium constant for copper II chelated to histidine is 18.3; for zinc

it is 6.7 to 12.9, depending on chelate structure (Ref. Chaberek and

Martell, Organic Sequestering Agents, Wiley & Sons, p.549). Because

these are exponential relationships, the real difference in the constants

is 10 to the 5th up to 10 to the 11th. Only glutathione, cysteine, and

thionein can intercept this Carnosine-copper transport, but that's one of

the big problems in autism, isn't it? These sulfur players have gone AWOL,

and copper is excessive at the expense of zinc. Dr. Bill Walsh has made

excellent presentations on this. You might think that Carnosine plus zinc

will act to put zinc in and take copper out. With these equilibrium

constants and with the natural copper content of food, that's very

unlikely. You need a million or more zinc atoms for each copper atom to be

competitive in this game! Histidine/Carnosine-copper wisdom has graduated

into medical textbooks. We're not talking about research papers; we're

talking what you should and shouldn't do per medical texts. Copper

homeostasis with histidine and

histidine-albumin complexes are well discussed by Danks, Chapter 58

of Stanbury et al, The Metabolic Basis of Inherited Disease, 5th Ed,

p.1252-1254.

For Carnosine, the publicity is a bit worse. Carnosine is a threat to

worsened 's disease because it and its sister anserine are such good

importers of copper to body tissues. Ref: Scriver CR and TL , Chapt 26

in Scriver et al eds, The Metabolic Basis of Inherited Disease 6th ed

McGraw-Hill (1989) 765.

Now, let's go to the really bad guy here, beta-alanine. To be concise:

beta-alanine 255 blocks renal conservation of taurine and causes

hypertaurinuria - loss of taurine in the urine. This, in turn, causes

urinary loss of magnesium, which worsens sulfotransferase activity as well

as lots of other necessary enzymatic processes. If you give Carnosine, you

lose taurine and magnesium. There are lots of references, but you can start

with Dr. Scriver's work referenced above, because all of this

biochemistry (Carnosine, beta-alanine, taurine, etc.) is closely related. "

----End of info from Dr. Panborn.----

********************************************************************************\

*****************************

Here is info on Dr. Chez's carnosine study:

Carnosine, a dipeptide, is sometimes presented as N-Acetylcarnosine. Doctor

Chez finds most beneficial a dosage of 400 mg Carnosine in combination with

50 IU Vitamin E and 5 mg zinc, twice a day. " It affected language,

receptive language, eye contact, communication, which are things children

with autism have big gaps with (sic), " Chez said. It is interesting to note

that, at least for adults, the dose is 1000 mg spread through the day, " for

the body automatically metabolizes lower amounts of Carnosine into an inert

substance, but the body cannot neutralize the 1000 mg " (Life Extension

Directory). Carnosine is the dipeptide of the amino acids histidine and

alanine, and functions primarily as a pH buffer in muscle tissue.

Unfortunately, muscle levels are reduced 63% between ages 10 and 70

(Stuerenburg). High Carnosine levels are associated with an increase in

physical performance especially anaerobic performance. Studies revealed

that Carnosine administration can benefit the immune responsiveness.

Carnosine is best known for its ability to buffer lactic acid in muscle

tissue and for its multiple antioxidant capabilities. When cells were

exposed to 90% oxygen, only Carnosine exerted significant protection. It

reduced the level of chromosomal damage by twothirds! It boosts levels of

free IGF1, a hormone necessary to maintain youthful cellular function

throughout the body. The present findings would indicate an

immunoprotective role of Carnosine, although definitive conclusions must

await the results of future studies. A study by Florida State University

reported that it helps modulate and protect essential nerves and membranes

from excessive zinc and copper toxicity. Since many autistic kids are

copper toxic, this may be why some are benefiting.

In some children, too high a dose may overstimulate some patient's frontal

lobes which can cause increased irritability, hyperactivity, or insomnia

which was observed already in hyperactive autistic 254 children. Other than

that, there were no side effects, Dr. Chez says.

Here's a comment from Willis S. Langford regarding Dr. Chez's vs. Dr.

Pangborn's opinion:

The amino acid alanine is required to use tryptophan and B6 properly. It is

needed for synthesis of pantothenic acid as well. However, as stated,

alanine inhibits taurine metabolism. Histadine is a powerful chelator and

can quickly deplete nutrients already in short supply. Nevertheless,

carnosine has been used very successfully in protecting against radiation

damage by boosting immune function in cancer patients.

[Guest guest]

Hello,

I can confirm that my son with autism and epilepsy does NOT tolerate at

all Carnosine- It led to total lack on concentration with the same

pronounced side effects that an anti-epileptic.

Lorene

R. Owen wrote:

> Hello everyone,

>

> I wrote a letter to Dr. Jon Pangborn and asked him his opinion regarding

> the use of carnosine in supplements, specifically Metagenics' new Zinlori

> product, which contains a low dose of carnosine (my letter is at the

> bottom

> of this message). Following is Dr. Pangborn's reply (which he stated

> that

> I could post to Internet Yahoo groups).

>

>

>

>

>

> Dear :

>

> I still have the same concerns about carnosine use as a supplement for

> autistics. I have spoken to Dr. Chez directly about it. I'm aware that it

> has helped many autistics, especially those with seizure conditions, and

> Dr. Chez confirms that the best responses he has seen are for seizure

> cases. I'm also aware of a number of disasters with its use - extreme

> hyperactivity, worsening of autistic traits, and week-to month periods of

> recovery after using carnosine for only one day.

>

> Autistics are individuals who have considerable variability when it comes

> to biochemistry that's on the periphery of that which pertains

> directly to

> autism itself. Carnosine is not central to autism; it is on the

> periphery.

> Carnosine is a peptide composed of histidine (a conditionally essential

> amino acid) and beta-alanine (often a troublemaking amino acid). Some

> manufacturer claims that I've seen exhibit total ignorance when they say

> carnosine is histidine plus " alanine " . Alanine is fine, beta-alanine is

> definitely not fine.

>

> So, if you want to try carnosine as a nutritional option, do so with the

> knowledge that adverse effects can occur. I must continue to advise

> against

> its use by clinicians until certain analytical (lab) measurements are

> negative for contraindication. Analytical contraindications for carnosine

> use are: elevated carnosine and/or beta-alanine in blood/urine, and high

> taurine (wasting) in urine. A further contraindication would be worsening

> of the blood copper/zinc ratio with carnosine despite co-supplementation

> with zinc.

>

> You may post this on the Internet.

>

> Jon Pangborn

>

________________________________________________________________________________\

_______________

>

________________________________________________________________________________\

_______________

>

> Dear Dr. Pangborn,

>

> I received your contact information from the Autism Research

> Institute. I

> have asked this question on a few well-respected and helpful autism

> lists,

> but no one knew the answer, so I am writing to you directly. I am a

> single

> parent of a 6 1/2 year old son with autism, and research quite a bit (at

> least a little every day). My goal is to choose the best supplements for

> my son. There is a relatively new product by Metagenics called

> Zinlori 75

> (other brands market it as PepZin), which sounds very promising for

> healing

> the gut. Here's the link:

>

> http://www.metagenics.com/products/catalog/detail.asp?pid=225

>

> Back when everyone was citing a study by Dr. Chez regarding carnosine, I

> found statements attributed to you (by searching on google and in a paper

> by Willis Langford--see the info below), and decided NOT to try carnosine

> for my son. Although I did not totally understand what was said in the

> references (I do not have a medical or biochemical background), the

> concerns seemed serious, so I didn't try the product.

>

> A well-informed parent on the chelatingkids2 list posted info about

> Metagenics' new Zinc/Carnosine complex. This parent has a relatively

> complex understanding of biomedical and is VERY well informed. He is

> really excited about this product and has posted links to a lot of

> studies

> regarding its efficacy.

>

> I am wondering if you still have reservations about carnosine, and

> specifically what you think about the new low dose carnosine/zinc complex

> (perhaps the dosage is key, and a little is Ok, as in low dose

> naltrexone,

> or LDN). I know that some DAN! practitioners are prescribing or

> recommending this product (I don't know which doctors, but listmates have

> reported this). Here's a link to an article about this complex (I will

> also send you the article in a separate email):

>

> http://www.iherb.com/ulcers2.html#intro

>

> Thank you in advance for any insight you can provide! I really

> appreciate

> your time and expertise. Also, would it be Ok to share the

> information you

> provide with the few lists and individuals I posted to (this included Dr.

> McCandless' CSB list and chelatingkids2)?

>

> Thanks again! :-)

>

>

>

> From a paper entitled " Mastering Autism " by Willis S. Langford:

>

> Dr. Pangborn, Ph. D. biochemist, has some serious reservations about Dr.

> Chez's approach to carnosine supplementation (referenced below).

>

> Dr. Pangborn has stated:

>

> " In body tissues, carnosine is split into histidine and beta-alanine.

> Beta-alanine can be a real troublemaker, and I'll get to that shortly.

> Histidine is the Dr. Jekyll and Mr. Hyde part. Histidine becomes

> formiminoglutamic acid (FIGlu), and FIGlu (an intermediate metabolite in

> histidine catabolism in the conversion of histidine to glutamic acid,

> with

> the formimino group being transferred to tetrahydrofolic acid) pushes the

> formation of 5-formiminotetrahydrofolate. A build up of FIGlu usually

> indicates a folic acid deficiency. (A test of vitamin B12 deficiency,

> folic

> acid deficiency, liver disease, or genetic deficiency of glutamate

> formiminotransferase, based on urinary excretion of FIGlu).

>

> This is good, even though it often raises FIGlu levels in the urine and

> blood of autistics. It's good because: (a) it helps remove a potential

> folate trap, and ( it leads to two forms of folate that are required

> for

> purine and purine nucleotide synthesis. One of these forms,

> 10-formyltetrahydrofolate, comes in just after the adenylosuccinase step

> and helps " pull " the process along at a documented sticking point for

> some

> forms of autism.

>

> However, histidine and Carnosine are powerful carriers of copper. They

> transport copper from the intestinal milieu into the portal blood, and

> from

> there to organs and tissues in the body. And don't think you can displace

> copper with zinc once the copper is on histidine--you cannot. The

> equilibrium constant for copper II chelated to histidine is 18.3; for

> zinc

> it is 6.7 to 12.9, depending on chelate structure (Ref. Chaberek and

> Martell, Organic Sequestering Agents, Wiley & Sons, p.549). Because

> these are exponential relationships, the real difference in the constants

> is 10 to the 5th up to 10 to the 11th. Only glutathione, cysteine, and

> thionein can intercept this Carnosine-copper transport, but that's one of

> the big problems in autism, isn't it? These sulfur players have gone

> AWOL,

> and copper is excessive at the expense of zinc. Dr. Bill Walsh has made

> excellent presentations on this. You might think that Carnosine plus zinc

> will act to put zinc in and take copper out. With these equilibrium

> constants and with the natural copper content of food, that's very

> unlikely. You need a million or more zinc atoms for each copper atom to be

> competitive in this game! Histidine/Carnosine-copper wisdom has graduated

> into medical textbooks. We're not talking about research papers; we're

> talking what you should and shouldn't do per medical texts. Copper

> homeostasis with histidine and

> histidine-albumin complexes are well discussed by Danks, Chapter 58

> of Stanbury et al, The Metabolic Basis of Inherited Disease, 5th Ed,

> p.1252-1254.

>

> For Carnosine, the publicity is a bit worse. Carnosine is a threat to

> worsened 's disease because it and its sister anserine are such

> good

> importers of copper to body tissues. Ref: Scriver CR and TL ,

> Chapt 26

> in Scriver et al eds, The Metabolic Basis of Inherited Disease 6th ed

> McGraw-Hill (1989) 765.

>

> Now, let's go to the really bad guy here, beta-alanine. To be concise:

> beta-alanine 255 blocks renal conservation of taurine and causes

> hypertaurinuria - loss of taurine in the urine. This, in turn, causes

> urinary loss of magnesium, which worsens sulfotransferase activity as

> well

> as lots of other necessary enzymatic processes. If you give Carnosine,

> you

> lose taurine and magnesium. There are lots of references, but you can

> start

> with Dr. Scriver's work referenced above, because all of this

> biochemistry (Carnosine, beta-alanine, taurine, etc.) is closely related. "

> ----End of info from Dr. Panborn.----

>

********************************************************************************\

*****************************

> Here is info on Dr. Chez's carnosine study:

> Carnosine, a dipeptide, is sometimes presented as N-Acetylcarnosine.

> Doctor

> Chez finds most beneficial a dosage of 400 mg Carnosine in combination

> with

> 50 IU Vitamin E and 5 mg zinc, twice a day. " It affected language,

> receptive language, eye contact, communication, which are things children

> with autism have big gaps with (sic), " Chez said. It is interesting to

> note

> that, at least for adults, the dose is 1000 mg spread through the day,

> " for

> the body automatically metabolizes lower amounts of Carnosine into an

> inert

> substance, but the body cannot neutralize the 1000 mg " (Life Extension

> Directory). Carnosine is the dipeptide of the amino acids histidine and

> alanine, and functions primarily as a pH buffer in muscle tissue.

> Unfortunately, muscle levels are reduced 63% between ages 10 and 70

> (Stuerenburg). High Carnosine levels are associated with an increase in

> physical performance especially anaerobic performance. Studies revealed

> that Carnosine administration can benefit the immune responsiveness.

> Carnosine is best known for its ability to buffer lactic acid in muscle

> tissue and for its multiple antioxidant capabilities. When cells were

> exposed to 90% oxygen, only Carnosine exerted significant protection. It

> reduced the level of chromosomal damage by twothirds! It boosts levels of

> free IGF1, a hormone necessary to maintain youthful cellular function

> throughout the body. The present findings would indicate an

> immunoprotective role of Carnosine, although definitive conclusions must

> await the results of future studies. A study by Florida State University

> reported that it helps modulate and protect essential nerves and

> membranes

> from excessive zinc and copper toxicity. Since many autistic kids are

> copper toxic, this may be why some are benefiting.

>

> In some children, too high a dose may overstimulate some patient's

> frontal

> lobes which can cause increased irritability, hyperactivity, or insomnia

> which was observed already in hyperactive autistic 254 children. Other

> than

> that, there were no side effects, Dr. Chez says.

>

> Here's a comment from Willis S. Langford regarding Dr. Chez's vs. Dr.

> Pangborn's opinion:

> The amino acid alanine is required to use tryptophan and B6 properly.

> It is

> needed for synthesis of pantothenic acid as well. However, as stated,

> alanine inhibits taurine metabolism. Histadine is a powerful chelator and

> can quickly deplete nutrients already in short supply. Nevertheless,

> carnosine has been used very successfully in protecting against radiation

> damage by boosting immune function in cancer patients.

>

>

>

>

>